Prostate Cancer Clinical Trial End Points: “RECIST”ing a Step Backwards

Abstract

Purpose:To relate clinical issues to the clinical manifestations of prostate cancers across disease states using the eligibility and outcome criteria defined by Response Evaluation Criteria in Solid Tumors (RECIST). Experimental Design: The manifestations of prostate cancer that characterize localized, recurrent, and metastatic disease were considered using the eligibility criteria for trials defined by RECIST. To do so, we analyzed the sites, size, and distribution of lesions in patients enrolled on contemporary Institutional Review Board^approved trials for progressive castrate and noncastrate metastatic disease. Prostate-specific antigen (PSA) levels were also assessed. RECISTdefined outcome measures for tumor regression were then applied to the metastatic patient cohorts, and separately to the states of a rising PSA (noncastrate and castrate) and localized disease. Results: Only 43.5% of men with castrate metastatic and 16% of noncastrate metastatic disease had measurable target lesions >2 cm in size. Overall, 84.4% of the target lesions were lymph nodes, of which 67.7% were z2 cm in the long axis.There are no target lesions in patients in the states of a rising PSA and localized disease, making them ineligible for trials under these criteria. PSAbased eligibility and outcomes under RECIST conflict with established reporting standards for the states of a rising PSA and castrate metastatic disease. The clinical manifestations of prostate cancer across multiple disease states are not addressed adequately using the eligibility criteria and outcomes measures defined by RECIST. Important treatment effects are not described. Conclusions: Trial eligibility and end points based solely on tumor regression are not applicable to the majority of the clinical manifestations of prostate cancers representing all clinical states. Treatment effects can be described more precisely if eligibility criteria are adapted to the clinical question being addressed and clinical state under study, focusing on the duration of benefit defined biochemically, radiographically, and/or clinically.

Prospective Study Evaluating Na18F PET/CT in Predicting Clinical Outcomes and Survival in Advanced Prostate Cancer

“…Prostate cancer progression is characterized by a variety of disease states, including clinically localized disease, rising-PSA noncastrate, rising-PSA castration-resistant, clinically metastatic noncastrate, and clinically metastatic castration-resistant (19). Bone metastases are a frequent manifestation, yet there is no accurate quantitative method for imaging prostate cancer metastases in bone (20).…”

Budgetary Impact on a U.S. Health Plan Adopting Abiraterone Acetate Plus Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer

“…3 More than 90% of advanced prostate cancer patients have bone metastases, and 57% have metastasis to soft tissue. 4 Nearly all metastatic prostate cancer ultimately becomes castration resistant-usually within 13-21 months from initiation of hormonal therapy among untreated patients [5][6][7] -at which point very few treatments have demonstrated an impact on patient survival.…”

The Association Between Measures of Progression and Survival in Castrate-Metastatic Prostate Cancer

“…This is because changes in radionuclide bone scan are difficult to quantify objectively and reproducibly (1), and changes in prostate-specific antigen (PSA) may be dissociated from clinical outcomes such that a post-therapy decline may not mean that the drug has ''worked'', and an increasing value that it has not. The situation is complicated further by the fact that the most widely used criteria, Response Evaluation Criteria in Solid Tumors (2), adapt poorly to the most common clinical manifestations of prostate cancer (3). Although dramatic responses associated with effective therapies can be identified with Response Evaluation Criteria in Solid Tumors, targeted approaches that stabilize or slow tumor growth and which are not cytotoxic, may not.…”